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Cognitive & brain health

The cognitive-enhancement corner spans Russian research peptides, longevity nootropics, and sleep interventions. A few have meaningful human data; most are preclinical or rest on small, hard-to-replicate studies. Here is the honest evidence, grouped by how it's used.

Nootropic peptides

The peptides marketed for focus, memory, and neuroprotection.

Semax, a seven-residue ACTH(4-10) analog, raises BDNF and trkBMEHFPGPheptapeptide · ACTH(4–10) analogBDNF ↑trkB ↑A 7-RESIDUE ACTH FRAGMENT · RAISES BDNF

Semax: a real Russian nootropic with an under-tested evidence base

An ACTH(4-10)-derived heptapeptide that raises BDNF and is a registered drug in Russia. The mechanism is credible — but the human evidence is small, single-country, and mostly uncontrolled.

Selank, a seven-residue tuftsin analog, modulates GABA as an anxiolyticTKPRPGPheptapeptide · tuftsin analogGABA modulationanxiolyticA 7-RESIDUE TUFTSIN ANALOG · CALMS VIA GABA

Selank: a non-benzodiazepine anxiolytic peptide, lightly tested

A tuftsin-analog heptapeptide that modulates GABA without being a benzodiazepine — and matched benzodiazepines in small Russian trials. The mechanism is credible; the evidence base is thin.

Dihexa and synaptogenesis — striking animal data, no human trialsPRECLINICAL ONLYexisting neurontarget neuronproposed new synapse — rodent & in-vitro dataDIHEXA · AN ANGIOTENSIN-IV–DERIVED “SYNAPTOGENIC” COMPOUND

Dihexa: a striking preclinical nootropic with zero human evidence

An orally-active angiotensin-IV–derived compound famous for building synapses “more potently than BDNF” in the lab. The animal data are real — but there are no human trials, and its c-Met growth-pathway mechanism raises unanswered safety questions.

P021 — neurogenesis seen in rodents, no human dataPRECLINICAL · NO HUMAN DATA?rodent brainnew neurons observedhumansno evidence at allP021 · NEUROGENESIS SEEN IN RODENTS, NOT PEOPLE

P21 (P021): a neurogenic peptide with real animal data and no human evidence

Marketed as “P21,” the compound is really P021 — a CNTF-derived peptide that boosts neurogenesis in rodents. There are no human trials, no approval, and a genuinely muddled name. A straight read of where the science stands.

COCHRANE VERDICT · ISCHAEMIC STROKEdeath or disability: no benefitnon-fatal serious AEs: possible increaseno effectPORCINE-BRAINPEPTIDE MIXTURECEREBROLYSIN · NEUROTROPHIC HYPOTHESIS, WEAK EVIDENCE

Cerebrolysin: what it is, and what the evidence actually shows

A porcine-brain-derived peptide mixture sold abroad for stroke and dementia — and pitched online as a nootropic. A straight read of the Cochrane reviews and the regulatory reality.

Longevity nootropics & compounds

The non-peptide brain-support compounds in the longevity toolkit.

ALPHA-GPC — TWO STRANDS OF EVIDENCEcognition signal (dementia trials)unresolved stroke-risk associationPromising but thin — with an open safety question

Alpha-GPC: What the Evidence Actually Shows

A cholinergic precursor with real dementia-trial data, weak ergogenic studies, and an unresolved 2021 stroke-risk signal.

Methylene blue is hormetic: low dose helps mitochondria, high dose flips pro-oxidantlow dose: pro-energetichigh dose: pro-oxidantdose →HORMETIC · THE DOSE IS THE WHOLE STORY

Methylene blue: the longevity 'biohack' that's actually a drug

Low-dose methylene blue has a plausible mitochondrial mechanism and a real single-dose memory signal — but it's an FDA-approved drug, not a supplement, its anti-aging claims are preclinical, and it can cause fatal serotonin syndrome with antidepressants.

STRENGTH OF EVIDENCE BY SOURCEbovine-cortex PS (older, positive)soy-derived PS (mixed, weaker)The source switch reshaped the evidence base.

Phosphatidylserine: Evidence for Memory, Cortisol, and Cognitive Health

A membrane phospholipid with real biology, older positive cognition data on a form you can no longer buy, and a weaker case for the soy-derived version sold today.

GOTU KOLA — HUMAN EVIDENCE BY INDICATIONVenousWound / scarCognitionLongevitystrongweakBar height = qualitative strength of human data, not effect size.

Gotu Kola (Centella asiatica): What the Evidence Actually Shows

Strong for venous insufficiency and topical wound healing; the cognition and longevity claims rest on thin, mixed data.

POPULATION SIGNAL vs SUPPLEMENT GAPDRINKING-WATER LITHIUMsuicide / dementia ratelithium in water →lower ratesLITHIUM OROTATE PILL0 controlledhuman trialscarrier claim unprovenPopulation association is not causation.

Lithium orotate: an intriguing population signal, almost no direct evidence

Trace lithium in drinking water tracks with lower suicide and dementia rates — but that's an association, and lithium orotate itself has essentially no controlled human trials.

Sleep, mood & the cognition link

Because sleep and anxiety drive cognition as much as any nootropic does.

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